Stem Cells Plus Donor Vein May Work for Bypass

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Extrahepatic portal vein obstruction was treated in a 10-year-old using a bypass graft engineered from a deceased-donor vein and the patient's own stem cells recellularized with endothelial and smooth muscle cells.

Note that the patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs.

A bypass graft engineered from a deceased-donor vein and the patient's own stem cells could be a solution for patients who don't have enough native vein to do the job, first-in-man results showed.

The vein, recellularized with endothelial and smooth muscle cells, successfully restored blood flow for a 10-year-old girl with portal vein obstruction, without complications or the need for immunosuppression, Suchitra Sumitran-Holgersson, PhD, of the University of Gothenburg, in Gothenburg, Sweden, and colleagues found.

The girl gained in mental function and grew substantially in the 9 months the engineered vein remained sufficiently patent, they reported online in The Lancet.

"Tissue-engineered vein segments could be a therapeutic option in cases of venous insufficiency, obstructed veins, or inadequate autologous veins," the Swedish group suggested.

The same technique might also work on arteries, which generally have better long-term results than veins or prosthetic materials when a vessel needs replacement in a procedure like coronary bypass surgery.

"Use of stem cell-derived tissue opens interesting new areas of research, including attempts to reproduce arteries for surgical use in patients with arteriovenous fistulas for dialysis or coronary bypass surgery," the researchers noted.

"One of the major limitations of bypass surgery anywhere in the body is lack of a suitable conduit," Edward Y. Woo, MD, director of the vascular laboratory at the Hospital of the University of Pennsylvania in Philadelphia, noted in an email.

"Having an autologous vessel for implantation would largely replace the utilization of prosthetic grafts, cadaveric grafts, or other conduits used when healthy autologous tissue is not available," he added.

Over the past 40 years, the field has gone from completely artificial materials like Gore-Tex and Dacron to chemically-treated bovine or other xenografts to allografts from organ donors to syngeneic grafts from patients' own blood vessels, explained Jonathan Bromberg, MD, PhD, chief of transplantation at the University of Maryland in Baltimore.

Autologous vein harvested from the neck is usually used for portal vein grafts, noted Milan Kinkhabwala, MD, chief of transplantation at Montefiore Medical Center in New York City.

"The advance of using a hybrid vein using an allogeneic donor with autologous cells is that the neck dissection is not required, and these veins could be manufactured when needed for use in this or other applications, such as arteriovenous fistula," he wrote in an email.

Harvesting veins does add some risk in terms of infection and swelling, agreed Timothy Gardner, MD, medical director of the Center for Heart & Vascular Health at the Christiana Care Health System in Newark, Del.

However, the patency reported in the proof-of-concept case was a concern, he noted.

"Graft failure as early as 1 year postop is not an acceptable outcome," he wrote in an email to ABC News and MedPage Today.

The researchers acknowledged that strictures and aneurysm formation may be potential problems with their technique.

Follow-up of the patient at 9 months showed narrowing of the graft, with a decrease in lumen from 8 mm to 4 to 6 mm, that required a second tissue engineered graft at 1 year.

The girl had originally been planned to get the standard meso-Rex bypass procedure to replace the extrahepatic portal vein with the umbilical vein, because the internal jugular veins weren't judged long enough to fit the bill.

When the umbilical vein was found to be small and only partly patent, she received the engineered vein that had been prepared as a rescue procedure.

The donor vein was put through multiple cycles of washing and incubation with chemicals to strip it of cells, then seeded inside and out with autologous endothelial and smooth muscle cells generated from stem cells in the girl's bone marrow. The process took 1 month altogether.

In the year after the first operation, the patient gained 2 inches in height (6 cm) and 11 lbs. in weight (5 kg). Her parents reported that she was more physically active -- taking more long-distance walks and doing light gymnastics -- and had improved articulated speech and concentrated better in school activities.

These results justified the substantial price for the personalized treatment, Martin Birchall, MD, and George Hamilton, MD, both of University College London, wrote in an accompanying editorial.

But the procedure is too long and complicated to ultimately succeed in the healthcare market or to be practical for larger numbers of patients, they argued.

While promising, they wrote, "one-off experiences such as the procedure they describe need to be converted into full clinical trials in key target populations, and delivered via straightforward, quality-controlled production processes if regenerative medicine solutions are to become widely used and accepted."

This article was developed in collaboration with ABC News.

The study was funded by the Swedish government.

Sumitran-Holgersson reported receiving royalties from Absorber AB, a company that developed the XM-ONE kit.

Birchall and Hamilton reported having no conflicts of interest to disclose.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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